Process for the simultaneous halogenation and fluorination of aromatic derivatives

The present invention relates to a process for the simultaneous halogenation and fluorination of aromatic derivatives substituted by at least one group containing a halogenoalkyl unit. It relates more particularly to a process for the halogenation of the aromatic nucleus and a simultaneous process for the fluorination of the said group by halogen/fluorine exchange.

The term "halogenation of aromatic derivatives" is understood as meaning the attachment of at least one chlorine or bromine atom.

The term "aromatic derivatives substituted by at least one group containing a halogenoalkyl unit" is understood as meaning any monocyclic or polycyclic aromatic derivative corresponding to the following general formula:

Ar--(A--CX.sub.1 X.sub.2 Y).sub.n (I)

in which:

Ar represents a monocyclic or polycyclic aromatic radical which may contain at least one substituent other than --(A--CX 1 X 2 Y) n ,

A represents a covalent bond, an oxygen atom or a sulfur atom,

X 1 and X 2 , which are identical or different, represent a halogen,

Y corresponds to hydrogen, a halogen or an optionally halogenated alkyl chain having 1 to 3 carbon atoms, the halogens corresponding to X 1 , X 2 and Y being identical or different, but at least one of them being other than fluorine, and

n is equal to 1 or 2 and preferably equal to 1.

For greater clarity, the halogen/fluorine exchange of the group containing a halogenoalkyl unit will be designated by the term "fluorination-exchange".

It has been known for a long time to subject aromatic derivatives substituted by at least one group containing a halogenoalkyl unit to fluorination-exchange in a hydrofluoric acid medium, and then to chlorinate the aromatic derivative substituted by at least one group containing a fluoroalkyl unit, in a second, independent step, in the presence of a chlorination catalyst such as, in particular, FeCl 3 , BF 3 (German Pat. No. 825,397) or Pt-on-alumina (German Pat. No. 1,034,609).

The fact that this is a two-step process has numerous disadvantages and, in particular, causes a loss of yield.

It has been possible, as described in Houben Weyl (volume 3, page 679), to carry out the chlorination and the fluorination-exchange in a single step using a catalyst such as antimony pentachloride in anhydrous hydrofluoric acid.

Those skilled in the art are very familiar with the properties of this catalyst, which behaves both as a chlorination catalyst and as a fluorination catalyst.

The process described above has the advantage of proceeding in a single step, but it requires the presence of a catalyst which cannot be recycled, and this presents problems of pollution from the technical point of view and problems of viability from the economic point of view.

The present invention, which overcomes the disadvantages of the prior art, relates to a single-step process for the halogenation and fluorination-exchange of aromatic compounds substituted by at least one group containing a halogenoalkyl unit, which comprises reacting the said aromatic compound with a halogen in liquid hydrofluoric acid. The hydrofluoric acid serves a dual purpose; it acts as a fluorinating agent for the substituent group on the nucleus and also acts as a solvent during the halogenation of the aromatic nucleus.

French Pat. No. 77/39,363, published under No. 2,375,169, which describes the preparation of perfluoroalkylbenzenes, is known in the prior art. In this process, the corresponding alkylbenzene is reacted with chlorine and hydrofluoric acid in the gas phase at high temperature. The temperature is generally between 350° and 600° C. It is specified in the said document that, above a certain temperature (generally above 450° C.), the fluorination reaction of the alkyl side-chain is accompanied by chlorination reactions of the benzene nucleus.

This chlorination reaction of the benzene nucleus thus appears to result from a parallel reaction involving the chlorine present in the medium, at a temperature above 450° C., the hydrofluoric acid not participating in the reaction. This is confirmed to those skilled in the art by East German Patent No. 15,100, which shows that, at high temperature, if chlorine is reacted with an alkylbenzene in the absence of hydrofluoric acid, derivatives chlorinated on the benzene nucleus are obtained in addition to the perchloroalkylbenzene. This is further confirmed by the analysis of this German patent in U.S. Pat. No. 3,816,287.

Thus, the prior art showed those skilled in the art that, to obtain the corresponding perfluoroalkylbenzene from an alkylbenzene, it was necessary to use on the one hand chlorine (at high temperature because the reaction was carried out without a catalyst), this chlorine giving secondary chlorination reactions on the nucleus in addition to the perchlorination reaction of the alkyl chain, and on the other hand hydrofluoric acid to replace the chlorine atoms of the perchloroalkyl chain with fluorine atoms.

By virtue of the present invention, which diverges very considerably from the interpretation acknowledged in the prior art, it has been possible to carry out the halogenation of an aromatic nucleus firstly without a catalyst and secondly without being obliged to use a high temperature.

These objectives are achieved by using a halogen in the presence of liquid hydrofluoric acid.

The present process can be used to halogenate the aromatic nucleus and exchange the halogens of the halogenoalkyl chain of any aromatic derivatives substituted by one or more groups containing a halogenoalkyl unit, irrespective of the other substituents present on the nucleus.

In fact, the aromatic nucleus can contain, for example, at least one halogen, hydroxyl group, nitro group, cyano group, isocyanate group, carboxyl group, alkyl or alkoxy group or phenyl or phenoxy group, in addition to the group containing a halogenoalkyl unit.

The halogen will be attached to the nucleus according to the substitution rules well known to those skilled in the art, as a function of the presence of ortho-, para- or meta-directing radicals.

The fluorination-exchange makes it possible to exchange the halogens of halogenomethyl, halogenomethoxy and halogenothiomethyl groups to give --CF 3 , --OCF 3 and --SCF 3 .

In the case of halogenoalkoxy and halogenothioalkyl groups, the exchange will take place on the carbon of the alkyl chain which is located in the α-position to the heteroatom.

Thus, the groups --OCCl 2 --CCl 3 and --SCCl 2 CCl 3 will be converted by fluorination-exchange to --OCF 2 CCl 3 and --SCF 2 CCl 3 .

On the other hand, the halogen atoms directly attached to the benzene nucleus are not affected by the fluorination-exchange.

The hydrofluoric acid used for the present invention is preferably anhydrous hydrofluoric acid.

The molar ratio of the hydrofluoric acid to the starting aromatic compound is preferably between 10 and 100. An appreciably larger quantity does not have an adverse effect on the invention.

The quantity of halogen used is fixed by those skilled in the art, taking into account whether the desired product corresponds to monohalogenation of polyhalogenation. For monohalogenation, the reaction is preferably carried out in the presence of a stoichiometric deficit of halogen, that is to say with a molar ratio of halogen to aromatic compound preferably of between 0.5 and 0.9. For polyhalogenation, it is preferred to carry out the reaction with an excess of halogen. The halogen can be employed in a sealed enclosure under autogenous pressure (generally 1 to 50 bar) or under atmospheric pressure, by bubbling, or in any other device known to those skilled in the art.

The temperature at which the reaction is carried out is preferably between -20° C. and 150° C.

If the temperature is to be above 20° C., the reaction will have to take place under pressure because the hydrofluoric acid must be liquid.

The reaction time varies from a few minutes to a few hours.

This reaction time varies with the number of halogen atoms which it is desired to attach to the nucleus, and also with the starting materials and the reaction temperature.

The final halogenated aromatic product is isolated, for example by distillation of the hydrofluoric acid, which can thus be recovered and recycled, this being an important advantage of the process of the invention. It can also be isolated by extraction with organic solvents well known to those skilled in the art.

Examples of products of the formula (I) which may be mentioned are: trichloromethylbenzene, metabistrichloromethylbenzene, trichloromethoxybenzene, parabistrichloromethoxybenzene, trichloromethylthiobenzene, chlorotrichloromethylbenzenes, fluorotrichloromethylbenzenes, dichlorobromomethylbenzene, tribromomethylbenzene, chlorotrichloromethoxybenzenes, fluorotrichloromethoxybenzenes, p-trichloromethylphenyl isocyanate, p-trichloromethylphenyl chloroformate, pentachloroethoxybenzene, pentachloroethylthiobenzene, paratrichloromethylphenol and 2-chloro-4-trichloromethylphenol.

Although the invention is not limited to these compounds, it has a particularly advantageous application in the halogenation and the fluorination-exchange of perchloroalkyl, perchloroalkoxy and perchlorothioalkyl aromatic derivatives such as, for example, trichloromethylbenzenes, trichloromethoxybenzenes and trichloromethylthiobenzenes.

The halogenated aromatic derivatives substituted by a fluoroalkyl group are used as synthesis intermediates in the pharmaceutical and plant protection industries.

The present invention will be understood more easily with the aid of the examples which follow, which are given by way of indication but without in any way implying a limitation.